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Synthetic biology

Recoding bacterial genomes

Nature Reviews Genetics volume 14, page 822 (2013)Cite this article

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In two new studies, Lajoie and colleagues recode and expand the genetic code of the Escherichia coli genome by incorporating non-standard amino acids (NSAAs). This allows the production of novel proteins, which has potential applications in areas such as biosafety, agriculture and medicine. In their first study, Lajoie et al. replaced the UAG stop codon with the synonymous UAA codon. They subsequently deleted the gene that encodes release factor 1, which mediates translational termination at UAG. This allowed them to re-introduce UAG and re-assign its function from that of a stop codon to one that incorporates chosen NSAAs. The resulting genetically recoded organism had increased resistance to bacteriophage T7 and was able to efficiently incorporate NSAAs. In their second study, the authors expanded on this work by re-assigning 13 rare codons in each of 42 highly expressed essential genes in 80 E. coli strains. Although this recoding was successful, most strains with recoded genes showed reduced fitness, which indicates that combining several recoded genes into one genome may not be feasible. Interestingly, they occasionally found that replacement of synonymous codons, such as that of CUU with UUG, did not produce the same effects as the native codon. Together, these studies show that recoding the bacterial genome is feasible and provide useful information for future genome-wide codon re-assignment designs.

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References

  1. Lajoie, M. J. et al. Genomically recoded organisms expand biological functions. Science 342, 357–360 (2013)

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  2. Lajoie, M. J. et al. Probing the limits of genetic recoding in essential genes. Science 342, 361–363 (2013)

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  1. Isabel Lokody
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Lokody, I. Recoding bacterial genomes. Nat Rev Genet 14, 822 (2013). https://doi.org/10.1038/nrg3629

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